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A Single Dose Clinical Trial to Study the Safety of ART-I02 in Patients With Arthritis

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02727764
Recruitment Status : Active, not recruiting
First Posted : April 5, 2016
Last Update Posted : November 14, 2018
Sponsor:
Collaborator:
Centre for Human Drug Research (CHDR)
Information provided by (Responsible Party):
Arthrogen

Brief Summary:
This study will evaluate the safety and tolerability of a single intra-articular administration of ART-I02 (AAV5.NF-kB.IFN-β), a recombinant adeno-associated virus (AAV) type 2/5 vector in subjects with Rheumatoid Arthritis (RA) or Osteoarthritis (OA) and active arthritis of the carpometacarpal (CMC), metacarpophalangeal (MCP), proximal interphalangeal (PIP), or distal interphalangeal (DIP) joints.

Condition or disease Intervention/treatment Phase
Arthritis, Rheumatoid Osteo Arthritis Genetic: ART-I02 Phase 1

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 12 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Single Dose Clinical Trial to Study the Safety of ART-I02 in Patients With Arthritis
Actual Study Start Date : April 20, 2017
Estimated Primary Completion Date : September 2022
Estimated Study Completion Date : September 2022

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Arthritis

Arm Intervention/treatment
Experimental: Cohort I
ART-I02 1.2x10e12 vg/ CMC joint, 1.2x10e12 vg/ MCP joint, 0.6x10e12 vg/ PIP joint or 0.3x10e12 vg/ DIP joint single intra-articular injection
Genetic: ART-I02
Single Intra-articular injection in the carpometacarpal (CMC), metacarpophalangeal (MCP), proximal interphalangeal (PIP), or distal interphalangeal (DIP) joint
Other Name: Recombinant AAV type2/5 containing a hIFN-b gene

Experimental: Cohort II
ART-I02 1.2x10e12 vg/ CMC joint, 1.2x10e13 vg/ MCP joint, 0.6x10e13 vg/ PIP joint or 0.3x10e13 vg/ DIP joint single intra-articular injection
Genetic: ART-I02
Single Intra-articular injection in the carpometacarpal (CMC), metacarpophalangeal (MCP), proximal interphalangeal (PIP), or distal interphalangeal (DIP) joint
Other Name: Recombinant AAV type2/5 containing a hIFN-b gene

Experimental: Cohort III
ART-I02 1.2x10e12 vg/ CMC joint, 1.2x10e13 vg/ MCP joint, 0.6x10e13 vg/ PIP joint or 0.3x10e13 vg/ DIP joint ART-I02 or maximum Tolerated Dose (MTD) as assessed in cohorts I and II: single intra-articular injection
Genetic: ART-I02
Single Intra-articular injection in the carpometacarpal (CMC), metacarpophalangeal (MCP), proximal interphalangeal (PIP), or distal interphalangeal (DIP) joint
Other Name: Recombinant AAV type2/5 containing a hIFN-b gene




Primary Outcome Measures :
  1. Treatment emergent (serious) adverse events [ Time Frame: Five years ]
    Treatment emergent (serious) adverse events


Secondary Outcome Measures :
  1. Change from baseline for clinical signs and symptoms of the target joint evaluated by the Composite Change Index (CCI) at week 1, week 2, week 4, week 8, week 12, week 16, week 20 and week 24 post administration of ART-I02. [ Time Frame: Baseline, week 1, week 2 , week 4, week 8, week 12, week 16, week 20 and week 24 post administration of ART-I02 ]
    Change from baseline of clinical signs and symptoms as measured by the aggregate score of the individual components of the CCI. Calculation of the CCI is based on changes of its components from baseline. The total CCI ranges from 0 (no effect or deterioration) to 10 (maximal effect). Successful treatment is defined as CCI ≥5.

  2. Change from baseline on synovitis and osteitis in the injected joint (target joint) evaluated by Magnetic Resonance Imaging (MRI) 12 and 24 weeks after administration of ART-I02 using the OMERACT RA MRI scoring system (RAMRIS). [ Time Frame: 12 and 24 weeks after administration of ART-I02 ]
    Change from baseline on synovitis and osteitis will be assessed by evaluating the aggregate scores of the components of the RAMRIS scoring system at week 12 and week 24. Synovitis will be assessed in three wrist regions (distal radioulnar joint, radiocarpal joint, intercarpal and carpometacarpal joints) and each MCP joint. Scale: 0-3 in increments of 33 % of the synovial compartment. Bone erosions will be assessed in each bone (wrists - carpal bones, distal radius, distal ulna, metacarpal bases; MCP joints - metacarpal heads, phalangeal heads) is scored separately . Scale: 0-10 in increments of 10 % of articular bone loss. Osteitis will be assessed by scoring each bone separately. Scale: 0-3 in increments of 33 % of bone oedema

  3. Vector DNA in whole peripheral blood, semen, urine, feces, and saliva [ Time Frame: Up to 24 weeks but maximally until such time that three consecutive samples have been tested negative ]
    To evaluate shedding of ART-I02 in blood, urine, faeces and saliva

  4. Induction of humoral immune responses against AAV5 by measuring antibodies against AAV5 and neutralizing antibodies against AAV5 at baseline, week 4 and week 24 post administration [ Time Frame: Baseline, week 4 and week 24 post administration ]
    To assess immune responses against adeno-associated virus serotype 5 (AAV5) after a single intra-articular dose of ART-I02

  5. Induction of humoral immune responses against hIFN-β by measuring antibodies against IFN-β and neutralizing antibodies against hIFN-β at baseline, week 4 and week 24 post administration [ Time Frame: Baseline, week 4 and week 24 post administration ]
    To assess immune responses against human interferon beta (hIFN-β) after a single intra-articular dose of ART-I02.

  6. Induction of cellular immune responses against AAV5 by measuring T cell responses against AAV5 at baseline week 4, 8, 12, 16 and week 24 post administration [ Time Frame: Baseline, week 4, 8, 12, 16 and week 24 post administration ]
    To assess T-cell response against AAV5

  7. Induction of cellular immune responses against hIFN-β by measuring T cell responses against hIFN-β at baseline week 4, 8, 12, 16 and week 24 post administration [ Time Frame: Baseline, week 4, 8, 12, 16 and week 24 post administration ]
    T-cell response against hIFN-β

  8. Improvement of the target joint will be assessed by extension and flexion evaluation [ Time Frame: Baseline, week 1, week 2, week 4, week 8, week 12, week 16, week 20 and week 24 ]
    To explore the response to a single intra-articular dose of ART-I02 by assessing MCP, PIP, DIP extension/ flexion.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion criteria

  1. Patients ≥18 years of age.
  2. Patient have to be diagnosed with RA according to the 2010 American College of Rheumatology/ European league against rheumatism (ACR/EULAR) criteria for the classification of RA, outlined in appendix B or OA as confirmed by their treating physician/specialist.
  3. Patient is scheduled for surgical intervention of the target joint.
  4. Inflammation of the CMC, MCP, PIP or DIP joint as confirmed by MRI.
  5. Written informed consent, able and willing to comply with the requirements of the study protocol.
  6. Judged to be in general good health with, in the opinion of the investigator, no other clinically significant and relevant abnormalities of medical history, and no abnormalities at the physical examination, vital signs, electrocardiography (ECG) and laboratory safety tests, performed at the screening visit and/or prior to administration of ART-I02.
  7. Females are not pregnant nor lactating. All patients use effective contraception in combination with barrier contraception for the first three months after administration or until three consecutive semen samples are negative.

Exclusion criteria

  1. Arthrodesis or joint replacement of the target CMC, MCP, PIP or DIP joint prior to inclusion.
  2. Known hypersensitivity to natural or recombinant hIFN-β, or to any excipients.
  3. Contra-indication for intra-articular treatment.
  4. Presence of neutralising antibody (Nab) titers against adeno-associated virus type 5 (AAV5) and/or hIFN-β.
  5. Active infectious disease of any nature, including clinical active viral infections.
  6. Previous treatment with an AAV-5 vector.
  7. Poor functional status, defined as being bed-bound.
  8. Participation in an investigational drug or device study within 90 days prior to screening or more than 4 times per year.
  9. Positive for human immunodeficiency virus (HIV) infection, hepatitis C antibodies or hepatitis B surface antigen.
  10. Positive for anti-double-stranded DNA antibodies (dsDNA).
  11. History of liver function abnormality requiring treatment, drug induced liver injury, chronic liver disease, excessive alcohol consumption or chronic alcohol induced disease.
  12. Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > 2 x upper limit of normal (ULN), or bilirubin > 2 x ULN. If a patient has AST or ALT > 2 x ULN but < 2.5 x ULN, re-assessment is allowed at the investigator's discretion.
  13. Severely impaired renal function (estimated glomerular filtration rate ≤ 30 mL/min according to the Cockcroft-Gault formula).
  14. Patient donated or lost approximately 500 ml blood within 4 months prior to the screening visit
  15. Mental condition rendering the patient unable to understand the nature, scope and possible consequences of the study and/or evidence of an uncooperative attitude
  16. Serious medical disease, such as severe liver or kidney disease, uncompensated congestive heart failure, myocardial infarction within six months, unstable angina, uncontrolled hypertension, severe pulmonary disease or active asthma, demyelinating neurological disease, depression or a history of depression, history of seizures or epilepsy, uncontrolled epilepsy, or history of cancer (other than cutaneous basal and squamous cell carcinoma or cervical intraepithelial neoplasia) with less than five years documentation of a disease-free state, recurrent opportunistic infections or other concurrent medical condition that, in the opinion of the investigator, would make the patient unsuitable for the study.
  17. Investigator has concerns regarding the safe participation of the patient in the trial or for any other reasons: the investigator considers the patient inappropriate for participation in the trial.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02727764


Locations
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Netherlands
Centre for Human Drug Research (CHDR)
Leiden, Zuid Holland, Netherlands
Sponsors and Collaborators
Arthrogen
Centre for Human Drug Research (CHDR)
Investigators
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Principal Investigator: Koos Burggraaf, PhD Principal Investigator
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Responsible Party: Arthrogen
ClinicalTrials.gov Identifier: NCT02727764    
Other Study ID Numbers: ART-I02-001-NL
First Posted: April 5, 2016    Key Record Dates
Last Update Posted: November 14, 2018
Last Verified: February 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Arthrogen:
Arthritis
Gene therapy
Phase Ib
Intra-articular
Additional relevant MeSH terms:
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Arthritis
Arthritis, Rheumatoid
Osteoarthritis
Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases
Connective Tissue Diseases
Autoimmune Diseases
Immune System Diseases